Abstract Direct ethanol fuel cells (DEFCs) are regarded as an attractive power source with high energy density, bio‐renewability, and convenient storage and transportation. However, the anodic reaction of DEFCs, that is, the ethanol oxidation reaction (EOR), suffers from poor efficiency due to the low selectivity to CO 2 (C1 pathway) and high selectivity to CH 3 COOH (C2 pathway). In this study, the selective EOR to CO 2 can be achieved at the Rh–SnO 2 interface in SnO 2 –Rh nanosheets (NSs). The optimized catalyst of 0.2SnO 2 –Rh NSs/C exhibits excellent alkaline EOR performance with a mass activity of 213.2 mA mg Rh −1 and a Faraday efficiency of 72.8% for the C1 pathway, which are 1.7 and 1.9 times higher than those of Rh NSs/C. Mechanism studies indicate that the strong synergy at the Rh–SnO 2 interface significantly promotes the breaking of CC bond of C 2 H 5 OH to form CO 2 , and facilitates oxidation of the poisonous intermediates ( * CO and * CH 3 ) to suppress the deactivation of the catalyst. This work not only provides a highly selective, active, and stable catalyst for the EOR, but also promotes fundamental research for the design of efficient catalysts via interface modification.